Health Economic Data Following Orthopedic Surgery for OFIRMEV® (Acetaminophen) Injection Published in Advances in Therapy

CHESTERFIELD, United Kingdom – Aug. 31, 2016 – Mallinckrodt Pharmaceuticals (NYSE: MNK), a leading global specialty pharmaceutical company, today announced new retrospective health economic data on OFIRMEV® (acetaminophen) injection that shows managing post-orthopedic surgery pain with the addition of OFIRMEV to the treatment regimen was associated with shorter length of stay (LOS) and decreased hospitalization costs compared to opioid use alone. OFIRMEV is indicated for the management of mild to moderate pain, management of moderate to severe pain with adjunctive opioid analgesics and reduction of fever in patients 2 years of age and older.

The manuscript, recently published online in Advances in Therapy, is titled "Comparative Analysis of Length of Stay and Inpatient Costs for Orthopedic Surgery Patients Treated with IV Acetaminophen or Opioids for Postoperative Pain." Researchers at the University of Washington conducted the analysis, which was supported by a grant from Mallinckrodt.

This retrospective cohort analysis of the Premier Inc. (Premier) inpatient hospital database from Jan. 1, 2009 to June 30, 2015 compared orthopedic surgery patients who received perioperative pain management combining intravenous (IV) acetaminophen and IV opioids to those who received only IV opioids starting on day of surgery and continuing up to the second day following surgery. The analysis included 485,895 orthopedic surgery patients from U.S. hospitals, with 174,805 patients (36%) receiving IV acetaminophen. Surgeries included total knee and hip replacements or revisions, fracture surgery and other orthopedic procedures.

"Multimodal analgesia is a treatment approach endorsed by numerous medical societies and The Joint Commission, and it is included in the American Pain Society guidelines for post-surgical pain management," said Steve Romano, MD, Senior Vice President and Chief Scientific Officer of Mallinckrodt. "OFIRMEV, which is used in a variety of surgical and non-surgical settings, can be an important component of a multimodal approach to manage acute pain."

"We observed significant economic differences in length of stay and hospitalization costs among orthopedic surgery patients whose pain was managed with a combination of IV acetaminophen and opioids compared to IV opioids alone," said Principal Investigator Ryan Hansen, Pharm.D., Ph.D., Research Assistant Professor of Pharmacy and Health Services (adjunct) at the University of Washington. "Real-world data such as this can help guide decision-making among health care professionals."

IMPLICATIONS OF THE DATA
This analysis may offer important insight on possible ways to help provide savings to the hospital system in the orthopedic surgical setting. These findings support a similar retrospective study published in 2015 in the orthopedic patient population.1

The differences observed between OFIRMEV and IV opioid monotherapy patients could be explained by unmeasured variables. Investigators attempted to account for this through the use of instrumental variable regression, adjusting models for potentially confounding variables, but unmeasured factors might still play a role in the associations reported.

The medication use data in the Premier database reflects the amount and dose charged rather than what was administered. However, systematic differences in billing of IV opioids between patients who did or did not receive OFIRMEV is not suspected.

The population of patients seen in Premier hospitals is not randomly sampled. Therefore, these results may not be generalizable outside of Premier hospitals. However, the database represents 20 percent of all hospitalizations in the U.S.

ABOUT OFIRMEV (Acetaminophen) Injection
OFIRMEV (acetaminophen) injection is indicated for the management of mild to moderate pain, management of moderate to severe pain with adjunctive opioid analgesics, and reduction of fever. OFIRMEV (acetaminophen) injection is the first and only intravenous (IV) formulation of acetaminophen to be approved in the United States. The U.S. Food and Drug Administration approved OFIRMEV in November 2010. OFIRMEV is available to hospitals and outpatient and ambulatory surgical centers across the U.S.

IMPORTANT RISK INFORMATION

WARNING: RISK OF MEDICATION ERRORS AND HEPATOTOXICITY

Take care when prescribing, preparing, and administering OFIRMEV Injection to avoid dosing errors which could result in accidental overdose and death. In particular, be careful to ensure that:

the dose in milligrams (mg) and milliliters (mL) is not confused;
the dosing is based on weight for patients under 50 kg;
infusion pumps are properly programmed; and
the total daily dose of acetaminophen from all sources does not exceed maximum daily limits.

OFIRMEV contains acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the recommended maximum daily limits, and often involve more than one acetaminophen-containing product.

CONTRAINDICATIONS

Acetaminophen is contraindicated in patients with:

- known hypersensitivity to acetaminophen or to any of the excipients in the intravenous (IV) formulation.
- severe hepatic impairment or severe active liver disease.

Common adverse reactions in adults include nausea, vomiting, headache, and insomnia. Common adverse reactions in pediatric patients include nausea, vomiting, constipation, pruritus, agitation, and atelectasis.

ABOUT MALLINCKRODT
Mallinckrodt is a global business that develops, manufactures, markets and distributes specialty pharmaceutical and biopharmaceutical products and therapies, as well as nuclear imaging products. Areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, nephrology, pulmonology and ophthalmology; immunotherapy and neonatal respiratory critical care therapies; analgesics and hemostasis products; and central nervous system drugs. The company's core strengths include the acquisition and management of highly regulated raw materials and specialized chemistry, formulation and manufacturing capabilities. The company's Specialty Brands segment includes branded medicines; its Specialty Generics segment includes specialty generic drugs, active pharmaceutical ingredients and external manufacturing; and the Nuclear Imaging segment includes nuclear imaging agents. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

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